Neoadjuvant Propranolol Plus SOX and Toripalimab for Locally Advanced Gastric/GEJ Adenocarcinoma

Starting soon · Phase 1/Phase 2

Conditions studied: Gastric or Gastroesophageal Junction Adenocarcinoma, Propranolol, SOX Chemotherapy, Toripalimab

In brief

This is a single-center, prospective, open-label, single-arm, phase Ib/II study evaluating the safety and efficacy of neoadjuvant propranolol combined with SOX chemotherapy and toripalimab in patients with resectable locally advanced gastric or gastroesophageal junction adenocarcinoma. A total of 49 participants will be enrolled. Stage 1 includes an initial safety lead-in of 12 participants, followed by efficacy evaluation using a Simon two-stage design. Participants will receive propranolol, toripalimab, oxaliplatin, and S-1 during the neoadjuvant period, followed by curative-intent surgery. The primary efficacy endpoint is pathological complete response. Secondary endpoints include safety and tolerability, major pathological response, R0 resection rate, event-free survival, recurrence-free survival, and overall survival. Exploratory analyses will assess changes in adrenergic stress markers, heart rate variability, peripheral immune parameters, β-adrenergic receptor signaling, and the tumor immune microenvironment.

Key facts

Study ID

NCT07727993

Run by

Ting Liu

People needed

49

Starts

2026-08-01

Expected to finish

2027-12-31

Last updated by the study team

2026-07-27

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Voluntary participation in the study, with written informed consent, and willingness and ability to comply with the study treatment and follow-up requirements.
• Male or female participants aged 18 to 75 years.
• Histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma.Resectable locally advanced disease as determined by imaging assessment or a multidisciplinary team according to the eighth edition of the American Joint Committee on Cancer staging system, generally defined as cT3-4a with any N category, or any T category with node-positive disease, corresponding to stage II-III disease, without distant metastasis.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Acceptable cardiopulmonary function, including all of the following:
• (1)No clinically significant abnormality on electrocardiography; (2)Resting heart rate of at least 60 beats per minute; (3)Systolic blood pressure of at least 90 mmHg; (4)No progressive or decompensated cardiopulmonary disease; (5)Left ventricular ejection fraction of at least 50%. 6.Adequate organ function during screening, defined as follows:
• Absolute neutrophil count of at least 1.5 × 10⁹/L;
• Platelet count of at least 75 × 10⁹/L;
• Hemoglobin level of at least 90 g/L;
• Total bilirubin no greater than 1.5 times the upper limit of normal;
• Aspartate aminotransferase and alanine aminotransferase no greater than 2.5 times the upper limit of normal;
• Serum creatinine no greater than 1.5 times the upper limit of normal or creatinine clearance of at least 50 mL/min;
• International normalized ratio no greater than 1.5 times the upper limit of normal, unless the participant is receiving stable anticoagulation and is considered eligible by the investigator.
• Female participants of childbearing potential must have a negative pregnancy test during screening. Male and female participants of reproductive potential must agree to use effective contraception during the study and for at least 6 months after the last dose of study treatment.

You may not qualify if…

• Distant metastatic disease confirmed by imaging or diagnostic laparoscopy, including but not limited to peritoneal, hepatic, or bone metastases, or positive peritoneal cytology.
• Previous systemic anticancer treatment for the current malignancy, including chemotherapy, immunotherapy, or targeted therapy, or previous radiotherapy. Diagnostic endoscopy and biopsy are permitted.
• Grade 2 or higher peripheral neuropathy at baseline.
• A second primary malignancy requiring systemic treatment within the previous 3 years, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, low-risk thyroid cancer, or other malignancies considered cured.
• Inability to tolerate curative-intent surgery or study treatment, as determined by the investigator.
• Active autoimmune disease, or a clinically significant history of autoimmune disease requiring systemic immunosuppressive treatment within the previous 2 years. Participants with type 1 diabetes mellitus, stable thyroid disease requiring replacement therapy, vitiligo, or grade 2 or lower psoriasis not requiring systemic treatment may be eligible.
• Use of systemic corticosteroids at a prednisone-equivalent dose of at least 10 mg/day, or other systemic immunosuppressive agents, within 14 days before the planned initiation of immunotherapy. Physiologic replacement therapy, inhaled or topical corticosteroids, and short-term prophylactic treatment related to surgery are permitted.
• Active infection, including but not limited to active tuberculosis, uncontrolled hepatitis B virus or hepatitis C virus infection, human immunodeficiency virus infection, or another serious infection requiring intravenous antibiotic treatment.
• Any contraindication to propranolol, including:
• (1)Bronchial asthma or a risk of bronchospasm; (2)Diabetic ketoacidosis or metabolic acidosis; (3)Severe or symptomatic bradycardia; (4)Second- or third-degree atrioventricular block, sinoatrial block, or sick sinus syndrome; (5)Cardiogenic shock; (6)Right-sided heart failure caused by pulmonary hypertension; (7)Congestive heart failure; (8)Clinically significant hypotension; (9)Prolonged fasting; (10)Severe peripheral circulatory failure; (11)Untreated pheochromocytoma; (12)Variant angina; (13)Concomitant treatment with rizatriptan benzoate. 10.Moderate or severe chronic obstructive pulmonary disease with a recent acute exacerbation.
• Active upper gastrointestinal bleeding at baseline, melena or hematemesis within the previous 4 weeks, bleeding requiring blood transfusion or endoscopic hemostasis, uncontrolled peptic ulcer disease, or a high risk of recent bleeding as determined by the investigator.
• Requirement for continuous full-dose anticoagulation, dual antiplatelet therapy that cannot be interrupted, or a bleeding disorder that cannot be adequately managed during the perioperative period.
• Known hypersensitivity to propranolol, oxaliplatin, S-1 or fluoropyrimidines, toripalimab, or any of their excipients, or a history of a severe adverse reaction to any of these agents.
• Concomitant use of medications that cannot be discontinued or replaced and that may cause clinically significant interactions with propranolol, including verapamil, diltiazem, class I or class III antiarrhythmic agents, strong CYP2D6 or CYP1A2 inhibitors, or other medications considered by the investigator to pose a major drug-drug interaction risk.
• Uncontrolled bleeding disorder, or major surgery or serious trauma within 4 weeks before enrollment, excluding the curative-intent surgery planned as part of this study.
• Pregnancy or breastfeeding, or unwillingness to use the required contraceptive measures.
• Any medical, psychiatric, social, or other condition that, in the investigator's judgment, may compromise participant safety, treatment compliance, or completion of the required follow-up, including severe psychiatric illness, substance abuse, or inability to attend scheduled visits.

Full record on ClinicalTrials.gov

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